SepsisCalc: Integrating Clinical Calculators into Early Sepsis Prediction via Dynamic Temporal Graph Construction

Sepsis is an organ dysfunction caused by a deregulated immune response to an infection. Early sepsis prediction and identification allow for timely intervention, leading to improved clinical outcomes. Clinical calculators (e.g., the six-organ dysfunction assessment of SOFA) play a vital role in sepsis identification within clinicians' workflow, providing evidence-based risk assessments essential for sepsis diagnosis. However, artificial intelligence (AI) sepsis prediction models typically generate a single sepsis risk score without incorporating clinical calculators for assessing organ dysfunctions, making the models less convincing and transparent to clinicians. To bridge the gap, we propose to mimic clinicians' workflow with a novel framework SepsisCalc to integrate clinical calculators into the predictive model, yielding a clinically transparent and precise model for utilization in clinical settings. Practically, clinical calculators usually combine information from multiple component variables in Electronic Health Records (EHR), and might not be applicable when the variables are (partially) missing. We mitigate this issue by representing EHRs as temporal graphs and integrating a learning module to dynamically add the accurately estimated calculator to the graphs. Experimental results on real-world datasets show that the proposed model outperforms state-of-the-art methods on sepsis prediction tasks. Moreover, we developed a system to identify organ dysfunctions and potential sepsis risks, providing a human-AI interaction tool for deployment, which can help clinicians understand the prediction outputs and prepare timely interventions for the corresponding dysfunctions, paving the way for actionable clinical decision-making support for early intervention.

Open-Set Heterogeneous Domain Adaptation: Theoretical Analysis and Algorithm

Domain adaptation (DA) tackles the issue of distribution shift by learning a model from a source domain that generalizes to a target domain. However, most existing DA methods are designed for scenarios where the source and target domain data lie within the same feature space, which limits their applicability in real-world situations. Recently, heterogeneous DA (HeDA) methods have been introduced to address the challenges posed by heterogeneous feature space between source and target domains. Despite their successes, current HeDA techniques fall short when there is a mismatch in both feature and label spaces. To address this, this paper explores a new DA scenario called open-set HeDA (OSHeDA). In OSHeDA, the model must not only handle heterogeneity in feature space but also identify samples belonging to novel classes. To tackle this challenge, we first develop a novel theoretical framework that constructs learning bounds for prediction error on target domain. Guided by this framework, we propose a new DA method called Representation Learning for OSHeDA (RL-OSHeDA). This method is designed to simultaneously transfer knowledge between heterogeneous data sources and identify novel classes. Experiments across text, image, and clinical data demonstrate the effectiveness of our algorithm. Model implementation is available at \url{https://github.com/pth1993/OSHeDA}.

SepsisLab: Early Sepsis Prediction with Uncertainty Quantification and Active Sensing

Sepsis is the leading cause of in-hospital mortality in the USA. Early sepsis onset prediction and diagnosis could significantly improve the survival of sepsis patients. Existing predictive models are usually trained on high-quality data with few missing information, while missing values widely exist in real-world clinical scenarios (especially in the first hours of admissions to the hospital), which causes a significant decrease in accuracy and an increase in uncertainty for the predictive models. The common method to handle missing values is imputation, which replaces the unavailable variables with estimates from the observed data. The uncertainty of imputation results can be propagated to the sepsis prediction outputs, which have not been studied in existing works on either sepsis prediction or uncertainty quantification. In this study, we first define such propagated uncertainty as the variance of prediction output and then introduce uncertainty propagation methods to quantify the propagated uncertainty. Moreover, for the potential high-risk patients with low confidence due to limited observations, we propose a robust active sensing algorithm to increase confidence by actively recommending clinicians to observe the most informative variables. We validate the proposed models in both publicly available data (i.e., MIMIC-III and AmsterdamUMCdb) and proprietary data in The Ohio State University Wexner Medical Center (OSUWMC). The experimental results show that the propagated uncertainty is dominant at the beginning of admissions to hospitals and the proposed algorithm outperforms state-of-the-art active sensing methods. Finally, we implement a SepsisLab system for early sepsis prediction and active sensing based on our pre-trained models. Clinicians and potential sepsis patients can benefit from the system in early prediction and diagnosis of sepsis.

MedVH: Towards Systematic Evaluation of Hallucination for Large Vision Language Models in the Medical Context

Large Vision Language Models (LVLMs) have recently achieved superior performance in various tasks on natural image and text data, which inspires a large amount of studies for LVLMs fine-tuning and training. Despite their advancements, there has been scant research on the robustness of these models against hallucination when fine-tuned on smaller datasets. In this study, we introduce a new benchmark dataset, the Medical Visual Hallucination Test (MedVH), to evaluate the hallucination of domain-specific LVLMs. MedVH comprises five tasks to evaluate hallucinations in LVLMs within the medical context, which includes tasks for comprehensive understanding of textual and visual input, as well as long textual response generation. Our extensive experiments with both general and medical LVLMs reveal that, although medical LVLMs demonstrate promising performance on standard medical tasks, they are particularly susceptible to hallucinations, often more so than the general models, raising significant concerns about the reliability of these domain-specific models. For medical LVLMs to be truly valuable in real-world applications, they must not only accurately integrate medical knowledge but also maintain robust reasoning abilities to prevent hallucination. Our work paves the way for future evaluations of these studies.

Inquire, Interact, and Integrate: A Proactive Agent Collaborative Framework for Zero-Shot Multimodal Medical Reasoning

The adoption of large language models (LLMs) in healthcare has attracted significant research interest. However, their performance in healthcare remains under-investigated and potentially limited, due to i) they lack rich domain-specific knowledge and medical reasoning skills; and ii) most state-of-the-art LLMs are unimodal, text-only models that cannot directly process multimodal inputs. To this end, we propose a multimodal medical collaborative reasoning framework \textbf{MultiMedRes}, which incorporates a learner agent to proactively gain essential information from domain-specific expert models, to solve medical multimodal reasoning problems. Our method includes three steps: i) \textbf{Inquire}: The learner agent first decomposes given complex medical reasoning problems into multiple domain-specific sub-problems; ii) \textbf{Interact}: The agent then interacts with domain-specific expert models by repeating the ``ask-answer'' process to progressively obtain different domain-specific knowledge; iii) \textbf{Integrate}: The agent finally integrates all the acquired domain-specific knowledge to accurately address the medical reasoning problem. We validate the effectiveness of our method on the task of difference visual question answering for X-ray images. The experiments demonstrate that our zero-shot prediction achieves state-of-the-art performance, and even outperforms the fully supervised methods. Besides, our approach can be incorporated into various LLMs and multimodal LLMs to significantly boost their performance.

Predictive Modeling with Temporal Graphical Representation on Electronic Health Records

Deep learning-based predictive models, leveraging Electronic Health Records (EHR), are receiving increasing attention in healthcare. An effective representation of a patient's EHR should hierarchically encompass both the temporal relationships between historical visits and medical events, and the inherent structural information within these elements. Existing patient representation methods can be roughly categorized into sequential representation and graphical representation. The sequential representation methods focus only on the temporal relationships among longitudinal visits. On the other hand, the graphical representation approaches, while adept at extracting the graph-structured relationships between various medical events, fall short in effectively integrate temporal information. To capture both types of information, we model a patient's EHR as a novel temporal heterogeneous graph. This graph includes historical visits nodes and medical events nodes. It propagates structured information from medical event nodes to visit nodes and utilizes time-aware visit nodes to capture changes in the patient's health status. Furthermore, we introduce a novel temporal graph transformer (TRANS) that integrates temporal edge features, global positional encoding, and local structural encoding into heterogeneous graph convolution, capturing both temporal and structural information. We validate the effectiveness of TRANS through extensive experiments on three real-world datasets. The results show that our proposed approach achieves state-of-the-art performance.

Rethinking Human-AI Collaboration in Complex Medical Decision Making: A Case Study in Sepsis Diagnosis

Today's AI systems for medical decision support often succeed on benchmark datasets in research papers but fail in real-world deployment. This work focuses on the decision making of sepsis, an acute life-threatening systematic infection that requires an early diagnosis with high uncertainty from the clinician. Our aim is to explore the design requirements for AI systems that can support clinical experts in making better decisions for the early diagnosis of sepsis. The study begins with a formative study investigating why clinical experts abandon an existing AI-powered Sepsis predictive module in their electrical health record (EHR) system. We argue that a human-centered AI system needs to support human experts in the intermediate stages of a medical decision-making process (e.g., generating hypotheses or gathering data), instead of focusing only on the final decision. Therefore, we build SepsisLab based on a state-of-the-art AI algorithm and extend it to predict the future projection of sepsis development, visualize the prediction uncertainty, and propose actionable suggestions (i.e., which additional laboratory tests can be collected) to reduce such uncertainty. Through heuristic evaluation with six clinicians using our prototype system, we demonstrate that SepsisLab enables a promising human-AI collaboration paradigm for the future of AI-assisted sepsis diagnosis and other high-stakes medical decision making.

Deconfounding Actor-Critic Network with Policy Adaptation for Dynamic Treatment Regimes

Despite intense efforts in basic and clinical research, an individualized ventilation strategy for critically ill patients remains a major challenge. Recently, dynamic treatment regime (DTR) with reinforcement learning (RL) on electronic health records (EHR) has attracted interest from both the healthcare industry and machine learning research community. However, most learned DTR policies might be biased due to the existence of confounders. Although some treatment actions non-survivors received may be helpful, if confounders cause the mortality, the training of RL models guided by long-term outcomes (e.g., 90-day mortality) would punish those treatment actions causing the learned DTR policies to be suboptimal. In this study, we develop a new deconfounding actor-critic network (DAC) to learn optimal DTR policies for patients. To alleviate confounding issues, we incorporate a patient resampling module and a confounding balance module into our actor-critic framework. To avoid punishing the effective treatment actions non-survivors received, we design a short-term reward to capture patients' immediate health state changes. Combining short-term with long-term rewards could further improve the model performance. Moreover, we introduce a policy adaptation method to successfully transfer the learned model to new-source small-scale datasets. The experimental results on one semi-synthetic and two different real-world datasets show the proposed model outperforms the state-of-the-art models. The proposed model provides individualized treatment decisions for mechanical ventilation that could improve patient outcomes.

Temporal Clustering with External Memory Network for Disease Progression Modeling

Disease progression modeling (DPM) involves using mathematical frameworks to quantitatively measure the severity of how certain disease progresses. DPM is useful in many ways such as predicting health state, categorizing disease stages, and assessing patients disease trajectory etc. Recently, with wider availability of electronic health records (EHR) and the broad application of data-driven machine learning method, DPM has attracted much attention yet remains two major challenges: (i) Due to the existence of irregularity, heterogeneity and long-term dependency in EHRs, most existing DPM methods might not be able to provide comprehensive patient representations. (ii) Lots of records in EHRs might be irrelevant to the target disease. Most existing models learn to automatically focus on the relevant information instead of explicitly capture the target-relevant events, which might make the learned model suboptimal. To address these two issues, we propose Temporal Clustering with External Memory Network (TC-EMNet) for DPM that groups patients with similar trajectories to form disease clusters/stages. TC-EMNet uses a variational autoencoder (VAE) to capture internal complexity from the input data and utilizes an external memory work to capture long term distance information, both of which are helpful for producing comprehensive patient states. Last but not least, k-means algorithm is adopted to cluster the extracted comprehensive patient states to capture disease progression. Experiments on two real-world datasets show that our model demonstrates competitive clustering performance against state-of-the-art methods and is able to identify clinically meaningful clusters. The visualization of the extracted patient states shows that the proposed model can generate better patient states than the baselines.

Cardiac Complication Risk Profiling for Cancer Survivors via Multi-View Multi-Task Learning

Complication risk profiling is a key challenge in the healthcare domain due to the complex interaction between heterogeneous entities (e.g., visit, disease, medication) in clinical data. With the availability of real-world clinical data such as electronic health records and insurance claims, many deep learning methods are proposed for complication risk profiling. However, these existing methods face two open challenges. First, data heterogeneity relates to those methods leveraging clinical data from a single view only while the data can be considered from multiple views (e.g., sequence of clinical visits, set of clinical features). Second, generalized prediction relates to most of those methods focusing on single-task learning, whereas each complication onset is predicted independently, leading to suboptimal models. We propose a multi-view multi-task network (MuViTaNet) for predicting the onset of multiple complications to tackle these issues. In particular, MuViTaNet complements patient representation by using a multi-view encoder to effectively extract information by considering clinical data as both sequences of clinical visits and sets of clinical features. In addition, it leverages additional information from both related labeled and unlabeled datasets to generate more generalized representations by using a new multi-task learning scheme for making more accurate predictions. The experimental results show that MuViTaNet outperforms existing methods for profiling the development of cardiac complications in breast cancer survivors. Furthermore, thanks to its multi-view multi-task architecture, MuViTaNet also provides an effective mechanism for interpreting its predictions in multiple perspectives, thereby helping clinicians discover the underlying mechanism triggering the onset and for making better clinical treatments in real-world scenarios.